Download Sample Oral Questions This file contains sample which have been

Sample Oral Questions
This file contains sample which have been presented to candidates for the Part 2 FRCPath
oral examination in Clinical Biochemistry. Candidates are given half an hour to prepare their
answers to a management problem and a laboratory scenario or clinical case.
After each case, the notes for the examiners have been provided by the examiner who set
the question. These are not intended to be exhaustive but provide some background for the
case. More importantly, they provide some insight for candidates into what the examiners
are looking for.
Questions for all candidates
Question 1
You are a fairly recently appointed head of Chemical Pathology in a district general hospital.
Since arriving you have implemented major changes in equipment and working practices.
Results for almost all tests can be available within an hour or so of the sample arriving in the
laboratory (depending only on how many other samples arrive at the same time), at any time
of the day or night.
What difference, if any will this make to the way you clinically validate results?
Question 1: Notes for Examiners
As with most management questions, there is no definitive right answer to this one - at least,
not until NICE tells us there is.
However, candidates should realise that there is a balance to be struck between holding
back results for clinical validation and the amount of time they are prepared to spend
validating. Factors which may influence this balance include:
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What happens to the results once they are clinically validated (eg. immediate electronic
transmission to wards and GPs vs printing and sending out on the next working day).
The number of people in the Department who are appropriately trained and qualified in
clinical validation. (Might this include technical staff following established protocols?).
The presence of modem links to permit clinical validation from home in the evenings
and at weekends. (Should staff who do this receive additional remuneration?).
The clinical needs of any specialist clinical units the DGH may house.
Whatever the local solution, two points seem clear:
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There is little point in improving analytical turnaround times to this extent if the results
are all held back for clinical validation on the next working day.
Releasing all results with no clinical validation stage raises some interesting questions
about the role of the consultant chemical pathologist/clinical scientist.
Question 2
You are Head of Chemical Pathology Services in a large District General Hospital. Your
Clinical Director is approached by the local Mental Health Trust who wish to discuss long
term support for their urine drugs of abuse (DOA) screening service.
The current situation in the Mental Health Trust is:
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they have a workload of 250 samples/week (200 from day clinics; 50 from inpatients.
they currently analyse all samples on site in the Drug Dependency Unit using nursing
staff trained by the instrument company.
they have a recently procured dedicated immunoassay system (throughput 50
samples/hr) and have entered into a favourable 3 year reagent rental contract covering
service, support and training.
they require a Monday-Friday with same day results for IP samples and next day results
for clinical samples.
they feel unable to support the above situation indefinitely and are worried about ‘quality
issues’.
they wish to negotiate MLSO staffing for their on-site analysis and associated quality
support from Chemical Pathology.
The Directorate supports the above in principle and you are asked to advise the Business
Manager on the key issues in respect of any future Service Level Agreement with the Mental
Health Trust. In doing this:
1.
What further information would you require about the current situation?
2.
What would be the key cost elements in the proposed ‘staff quality’ package?
3.
What quality standards might be incorporated into the agreement and how could they
be monitored?
Question 2: Notes for Examiners
1.
Extra information on current situation could include:
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2.
Cost Elements could include:
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3.
DOA profile required
Policy for any confirmatory analyses (if required)
Peaks and troughs of workload
Transport arrangements
Report validation procedures
Mode of transmission of reports
Standard of ‘laboratory’ facilities in the Drug Dependency Unit.
MLSO staffing:
- state registered staff will be needed (working unsupervised)
- workload suggests half-day commitment on M-F basis is necessary
- cost of 0.5 wte MLSO 1 is approximately 8K pa + on-costs
Quality Support:
- QC materials and documentation (if not in reagent contract)
- EQAS participation costs
Requirement for consultant advice (if any)
Financial agreement for accommodating growth/reduction in workload
Quality Standards and Monitoring
Important to realise that both parties can incorporate these.
User (Mental Health Trust) may include:
ƒ Provider laboratory CPA status
ƒ Turn around times (how define??) – including any requirement for urgent
analysis
ƒ EQAS performance
Provider (Pathology) may include:
ƒ Minimum acceptable ID for samples and request forms
ƒ Deadline for sample delivery (to meet agreed TAT)
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Monitoring Arrangements
Monthly Report (activity; standards compliance etc.)
Audit of specific aspects as necessary
Candidates may well wish to propose a longer term strategy of performing the work in the
central laboratory rather than a POCT exercise.
In making their response, candidates should show an awareness of the guidelines of the
Joint Working Party or Quality Assurance (POC Testing) and the CPA standard requiring
compliance with these.
Question 3
You receive a call from the ‘Customer Services Manager’ of your hospital saying that she
has received a formal written complaint from the parents of a child being treated by the
oncology firm. It concerns the clinical chemistry laboratory and she needs some information.
The gist of their complaint is that their son had to remain in hospital for an additional night
because the result for a specimen sent to the laboratory, for a Methotrexate analysis, was
not received in the late afternoon, when they had been promised it, but the following day.
The medical staff had told them that the specimen, which had been taken in the early
morning, would be analysed that day and that if the result was within their acceptable target
range, as they expected, their son would be discharged. The lateness of the result had
caused great distress to both the child and the parents together with the added
inconvenience of an extra night at the hospital and the additional expense.
Methotrexate analyses are not performed by your laboratory but sent to a neighbouring
hospital about 5 miles away, usually by taxi. Your preliminary investigation reveals that the
specimen was received by your specimen reception at 09.15h on the morning in question
but had not been sent to the referral laboratory. It had been discovered in a refrigerator in
the late afternoon after a phone call from the requesting doctor who was trying to obtain the
result. The specimen had been sent for analysis the following morning, and the result was
within the target range.
What further information would you require to investigate the complaining in more depth?
What steps would you take to ensure that the same problem did not happen again?
You will be expected to draft a letter on behalf of the Chief Executive, who replies to all of
the formal complaints received by the hospital. How will you word this letter?
Question 3: Notes for Examiners
1.
Further information
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2.
Preventing a repeat of the problem
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3.
What was the standard procedure for sending Methotrexate specimens away?
Was there a written protocol?
Who had the responsibility for sending the specimen?
Why had the specimen not been sent away?
¾ Too busy
¾ Inexperienced staff
¾ Poor training
¾ Etc
Was the area being supervised?
Why was it placed in the refrigerator?
At the end of the investigation, what actually did go wrong?
Ensure correct training for all who undertake specimen reception.
Written procedures for all specimens sent away.
Adequate supervision for this crucial area.
Reminder to all staff of the vital nature of the work in specimen reception.
Sharing of the complaint with all staff, avoiding a ‘who’s to blame’ approach.
Chief Executive’s letter
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Apologise for the error, since the laboratory was to blame.
Explain in outline what went wrong.
Give mitigating circumstances if there were any.
Explain that procedures have been put in place to prevent it happening again.
Offer to talk to the parents or show them around the laboratory.
There are many avenues that can be explored with this case.
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Methotrexate treatment and regimes.
‘No blame’ culture vs. the witch-hunt.
The response of the individual who made the mistake.
The likelihood of the mistake happening again.
Errors often being a combination of circumstances.
Completing an ‘incident report’.
Who should perform the investigation?
Learning from mistakes.
Etc.
Question 4
You are three months into your Consultant appointment at a large District General Hospital.
Thus you are perceived by your Clinical Director to be ‘new blood’ and are asked to be one
of two Pathology representatives (the other is a Consultant Histopathologist) on the Trust’s
established General Practitioner (GP) Liaison Group. This meets every two months to
review clinical and support services provision by the Trust.
After two meetings it is clear that there is general dissatisfaction with the Pathology services
and Chemical Pathology seems to be singled out for much non-specific criticism. (‘Too slow’
and ‘unhelpful’ are familiar comments from the more vociferous GP’s).
In subsequent discussion with the Clinical Director you express your concerns and
‘volunteer’ to conduct a formal review of user satisfaction among the GP’s as the basis for
changes in service provision.
In planning this exercise:
What approaches to gathering the required information would you consider and why? From
your experience, what do you feel will be the key aspects of the services to GP’s on which
you will need to seek opinion?
Question 4: Notes for Examiners
It is likely that we would all have slightly different approaches to this problem but candidates
might consider the following points:
Approaches to Gathering Information
Background
Existence of any current service agreement and standards.
Previous audits (if any) of service to GP’s
Formal log of complaints from GP’s (general or discipline specific)
New Information
Audit of current service
Questionnaire – validity? Design?
Visits to selected GP’s (possibly with questionnaire)
Views of laboratory staff
Aspects of Service for User Opinion/Level of Satisfaction
May include:
Access (‘opening hours’)
Request form design (personalised; multidisciplinary)
Phlebotomy Services (?domiciliary visits)
Turnaround times
Transport of Samples and Reports
Availability of Consultant advice
Electronic Data Interchange
POCT Support
Management data on Pathology usage by practice
CPA Status (awareness!)
Participation in Clinical Audit
Pathology handbook/Information sheets/CD (covering much of the above information)
Some of the above will require an overall opinion, others (eg. consultant advice) may require
discipline specific information.
Question 5
You are informed by the Laboratory Manager that the Trust is suffering long ‘trolley waits’
and is reorganising its Medical Admissions Unit (MAU) to enable better patient management.
A Nurse Consultant has recently been appointed as part of this initiative. She has stated it
is necessary for MAU to have a “machine that does D-Dimers and Troponins” to enable early
discharge.
Develop your view of this information. What are the implications for patients, the Trust and
the laboratory?
The Medical Policy Board decides that it needs the laboratory perspective. You are asked to
attend one of their monthly meetings to inform them prior to their making a decision. Draft
your submission highlighting the points to be made.
Question 5: Notes for Examiners
While a number of approaches are possible reflecting local practice the essential
components of the candidate response should focus around recent National (MDA guidance)
and publications on the utility (or otherwise) of such testing.
The candidate should be aware that:
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The Medical Devices Agency have issued guidance on point of care testing (POCT)
which informs current practice.
There are cross-discipline issues and they need to liase with their Haematology
colleagues.
The need to tactfully approach the Nurse Consultant as the information is indirect.
Clinical decisions are ultimately the responsibility of the Medical Consultants and they
therefore need to elicit their views. They need to obtain their perspective of the MAU.
Issues such as turnaround time and IT (patient records, contiguity, the electronic patient
record) are high relevant.
The impact on the laboratory service of supporting POCT training, maintenance and
supervision.
The economics of the proposal (at different levels: direct cost, impact on unit, impact on
Trust, societal implication)
The need for a concise response setting out the position adopted incorporating
timeliness, cost, staffing and training implications.
The need for the use of management structures to effect input.
Risk and Clinical Governance issues underpin such decisions.
Question 6
As the newly appointed head of clinical biochemistry you are called to see your clinical
director. The contract for your main endocrine immunoassay analyser system is due for
renewal in a year’s time. Under pressure to make cost savings, the Pathology Directorate
decides to take this opportunity to amalgamate the immunoassay functions of all the
departments. As a result of a “process re-engineering study”, the director has taken the
irrevocable decision to undertake all the immunoassays formerly performed in the separate
departments of haematology, clinical biochemistry, immunology, virology and microbiology in
one laboratory area on the minimum number of new analysers. You are charged with
drawing up a specification for the clinical chemistry analytical performance and implementing
the changes. Indicate how you will deal with this within the time frame. What important
elements must be retained to ensure service quality is not compromised by the new
arrangements?
Question 6: Notes for Examiners
In a sense this is a gift to anyone who has had a part in change management, or works in
immunoassay. However, candidates need to be able to see the bigger picture and work
logically, even if they have never met the situation suggested in this scenario. There are a
number of aspects to this question.
Specifying and selecting analytical system within time frame.
Need to draw up specification – workload, turnaround, speed of analysis, minimum volume,
analytical performance (CV, EQA data, calibration frequency, etc), random access, add on
tests, stats, assay list (which Troponin, hCG specificity) etc, etc.
Needs to be tendered through European Journal advert (for candidates from EEC!).
Timeframe should include allowance for seeing systems in hospitals, testing system etc. Need
for redundancy in number of analysers to avoid downtime (?critical assays – troponins, hCG,
etc).
Need to produce test script to test responses to tender against specification. How to deal
with special tests – eg. IGF, GH, vitamin D, bone markers, rarer steroids etc not on standard
platforms.
Need to define show-stoppers in terms of what is impossible (eg. workload incompatible with
proposed configuration, (unable to perform stat hCG or Troponin for example.
Suitability of cross-discipline platforms
Compatibility of sample types.
Any precautions for high risk work (virology, etc) in mixed samples.
Ability to work random access or pseudo-batch.
Best of breed for all disciplines possible?
Arrangements for cross-discipline working
Working practices in each department, (eg. add-on-tests, follow-up tests).
Numbering systems and booking samples in.
Grade and training of staff operating analysers.
QC and calibration practices.
Sample storage (eg. paired sera for virology).
Authorising results from analyser and finished reports – different practices in different
departments.
Implementing the change
(This is the key) – need for clear leadership and management structure for both
implementing change and running new section.
Perhaps need to question idea of changing laboratory practices and analysers at the same
time (forced to by resources but better not both at once).
Dedicated, experienced leadership essential at BMS and senior management level.
Training needs.
Visiting successful combined laboratories eg. The Netherlands, USA.
Communication, communication, communication!
Questions for medical candidates
Question 1
A 47 year old man presented to his GP with eruptive xanthomata over his elbows and hips.
The GP arranged for fasting lipids to be measured:
Cholesterol
Triglyceride
HDL Cholesterol
17.4 mmol/L
28.8 mmol/L
0.5 mmol/L
He was referred to the local Lipid Clinic, and in the course of investigation for secondary
causes of hyperlipidaemia he was found to have abnormal thyroid function tests:
Free T4
TSH
3 pmol/L
0.91 mIU/L
(10-24)
(0.5-6.0)
His identical twin brother was also screened and found to have very similar lipid and thyroid
function test results.
How would you investigate these patients and what recommendations would you make
about their management?
Question 1: Notes for Examiners
There are two aspects to this problem: the mixed hyperlipidaemia (which is reasonably
straightforward) and the odd thyroid function tests (which we have still not explained
satisfactorily).
Candidates should be aware of secondary causes of hyperlipidaemia and of the need to try
lifestyle changes before considering pharmacological treatment. In fact both of these
patients were still living with their mother and consuming a fairly unhealthy diet. Their
weekly beer intake was around 14 pints each and they were not taking much exercise. They
were advised accordingly and complied enthusiastically, so that drug treatment for the
hyperlipidaemia was unnecessary. The xanthomata present in the first twin had virtually
disappeared when I last saw him.
It is important to treat patients and not laboratory tests, so I would expect candidates to want
more clinical information with regard to endocrine status. Neither man appeared to be
hypothyroid. The only unusual points in their past medical history is that they both had
Perthes disease as infants and they were considered to be ‘educationally subnormal’ and
were educated in a special school. However, they both have engaging personalities and are
both able to hold down jobs. They appear fit and well and have normal secondary sexual
characteristics.
The first question thus seems to be are the thyroid results correct?
The TFTs were consistently abnormal using the in-house assay (Bayer Immuno 1), even
when the samples were no longer lipaemic. Tests for heterophile antibody interference were
negative. The Free T4s and TSHs were confirmed in another lab by a different commercial
assay, and the Free T4 was also found to be low by an equilibrium dialysis method.
The TFT results seem to be genuine, so a pituitary cause seems to the next most likely
explanation, even in the absence of any clinical evidence. Baseline pituitary hormones have
all been normal, and response to intravenous Synacthen was also normal. This is as far as
we have got to date – please note down any pertinent ideas from good candidates!
Question 2
Routine checking of the overnight emergency results reveals the following results obtained
from an 80 year old woman admitted the previous evening. The clinical details are “?
Obstruction”.
Na
K
Urea
Creatinine
ALT
Alkaline Phosphatase
Total Protein
Albumin
Bilirubin
Calcium
Glucose
115
2.8
12.9
81
26
64
67
42
18
2.39
7.2
mmol/L
mmol/L
mmol/L
umol/L
IU/L ( 9-52)
IU/L ( 36-125)
g/L
g/L
umol/L
mmol/L
mmol/L
A TSH had also been requested.
On contacting the ward, you discover the patient has a four week history of abdominal pain
and has suffered from profuse vomiting for a week. She was admitted because she had
become confused. The houseman had diagnosed SIADH, possibly secondary to gastric
carcinoma and had put the patient on fluid restriction but the Registrar is not so sure and
asks for your help.
How would you investigate this patient and what suggestions would you make about
management?
Question 2: Notes for Examiners
I would expect the candidates to want to know her fluid status (put on Dextrose, saline 1L
over 16 hours but had not yet passed urine, clinically rather flat but not markedly
dehydrated).
The clinical picture is one of gastric outlet obstruction, which had been recognised by the
medical team. They thought she might have a gastric carcinoma and this was causing
SIADH and hence the fluid restriction therapy.
However, this was unlikely as
adenocarcinomas tend not to be associated with SIADH and her results suggested a degree
of dehydration with a high albumin and urea for someone who had not been eating for
weeks. Further, she has other reasons for low potassium concentration, from alkalosis due
to loss of gastric acid and her drug therapy could cause the hypernatraemia. Finally if we
accept she was significantly dehydrated, then she may have elevated ADH due to volume
contraction from prolonged fluid loss enhancing water retention and causing relative
hyponatraemia.
I would expect the candidate to:
1.
2.
3.
4.
5.
Recognise this is unlikely to be SIADH and violates most of the principles underlying
the definition of SIADH.
Suggest that the original therapy (fluid restriction) is potentially dangerous in a patient
who has had significant fluid loss.
Be able to discuss the pathophysiology of the electrolyte response to prolonged
vomiting.
Recognise the effects of drugs (and ask about them).
Recognise the need to suggest therapeutic changes to medical colleagues
diplomatically!
I recommended checking her urine osmolality and sodium loss on a stat urine as I was sure
she would be conserving it as much as possible given her drug therapy. I suggested she
needed N saline with potassium IV to maintain her urine output and slowly raise her sodium.
Fluid restriction was not indicated in a patient who was vomiting. If she had untoward
sodium loss I would have measured a cortisol although this was not a typical picture of
Addison’s crisis and I checked the TSH as hypothyroidism could have complicated the
picture.
Her TSH was normal. We never received a urine sample and her electrolytes approached
normal in a couple of days on IV fluids alone, although her sodium has remained slightly low
(they have now stopped her drugs so it may rise further). Her albumin dropped to 32 g/L
once adequately hydrated emphasising her original fluid deficit may have been more than
was apparent clinically.
The gastroscopy showed severe erosive duodenitis but no
malignancy and she stopped vomiting once her oral intake was stopped. She is now
awaiting rehabilitation although it may be delayed as she slipped in the bathroom and
banged her head!
Question 3
You are the most senior person in the laboratory when, at 5.15 pm on a Monday evening,
the MLSO in your automated section brings you the following results on a 26 year old
woman on a gynaecology ward.
Serum
Sodium
Potassium
Urea
Creatinine
Glucose
108
4.2
21
130
6.2
mmol/L
mmol/L
mmol/L
umol/L
mmol/L
TSH
Free T4
<0.1
>50
mIU/L
pmol/L
You find the request form: the clinical details are ‘hyperemesis gravidarum, agitated’. The
patient administration system records that she was admitted late that morning.
What action do you take?
Question 3: Notes for Examiners
This woman was admitted in July, under the circumstances described. There are a whole
host of possible answers that we could consider acceptable but clearly candidates must
appreciate first that this woman is gravely ill and second that she may not be in the best
place. I rang the Gynae SHO whose bleep number was on the form and explained that (a)
this woman was thyrotoxic (b) severely hyponatraemic and thus (c) should be referred
immediately to the physicians with a view to further management in the ITU.
Having established this, the candidate could then be invited to discuss the principles of
management: it might be, for example, that the physicians were busy in A&E and would be
unable to see her for an hour. In that case, it could reasonably be expected that the
Chemical Pathologist should initiate immediate treatment . If that is the case he or she must
go and see the patient (I hope that they would want to anyway).
Although from the history the probability is that the hyponatraemia is secondary to vomiting
and inadequate sodium intake, the candidate should think about whether the lab can
measure her cortisol urgently.
Details of management will depend on clinical assessment of course and candidates should
be able to consider the principles which are straightforward, eg. cessation of any hypotonic
fluid, very careful provision of hypertonic saline with regular biochemical, physiological and
neurological monitoring, drugs to control vomiting (and fitting if necessary) for the
hyponatraemia and anti-thyroid drugs, iodine, dexamethasone and beta-blockade for the
thyrotoxicosis (if confirmed clinically).
The discussion might then lead to the dangers of severe hyponatraemia and its treatment,
and/or the nature of thyrotoxic crisis – often of very sudden onset, precipitated by
intercurrent illness, vomiting, etc. in a patient who may not have been diagnosed as
hyperthyroid before.
Question 4
A 24 year old woman weighting 60 kg is admitted to hospital with an acute abdomen. She is
diagnosed as having superior mesenteric artery thrombosis. Attempts to restore perfusion
are in vain and she develops irreversible bowel ischaemia, necessitating resection of the
small gut from a point 20 cm distal to the duodenal-jejunal junction, to a point 50 cm proximal
to the ileocaecal junction, with construction of the jejunoileal anastomosis.
You will be asked to advise on her immediate and longer-term management from the point of
view of maintaining fluid and electrolyte balance, and ensuring maintenance of her
(previously good) nutritional status.
You may further be asked how this management would differ from that of a patient who has
had a jejunostomy constructed.
Question 4: Notes for Examiners
These notes are fairly comprehensive – but general principles more important than detail.
Note that this patient does not have a jejunostomy. Preservation of the colon allows
considerable absorption of fluid and although IV fluid supplementation will be required until
bowel sounds return, it may not be required long term. The preservation of the ileocaecal
value is also significant, as it may delay transit and increase the time for absorption of fluid
(an nutrients) in the small gut. Nevertheless, diarrhoea is often a problem, and patient’s oral
free fluid intake should be limited; drugs such as Loperamide (to reduce intestinal mobility)
may be helpful.
With less than 50 cm of jejunum, this patient is likely to require long term parenteral nutrition,
but it is important to introduce early enteral feeding as much as can be tolerated. This helps
to preserve the integrity of the gut and promotes adaptation in the ileum.
Malabsorption is usually a continuing problem, and nutrient intake must take account of this.
A diet high in polysaccharides is recommended. These undergo fermentation in the colon to
short chain fatty acids, which provide a valuable source of energy (NB hazard of D-lactic
acidosis). A high fat intake will cause steatorrhoea, reducing transit time and water and
mineral absorption in the colon but medium chain fatty acids can be reabsorbed from the
colon. Diarrhoea and steatorrhoea may significantly reduce the amount of food/enteral
supplements that a patient is willing to consume.
Oxalate urinary calculi are a recognised hazard and the diet should be low in oxalate.
Vitamin supplementation is usually required.
In patients with a jejunostomy, the major early problem is fluid loss. Intravenous
replacement is always required – stoma output can be up to 8L/24h and is exacerbated if
oral fluids containing inadequate sodium are given. The concentration of sodium in oral fluid
should be 100-120 mmol/L and the addition of glucose facilitates sodium and water uptake.
Loperamide and drugs to reduce secretion (Omeprazole, Octreotide) are often useful.
Magnesium supplementation is usually required, potassium supplementation may be.
Long term parenteral nutritional support is always required with less than 75 cm of jejunum,
but in addition to whatever enteral intake is possible. Patients with up to 200 cm jejunum
usually require enteral supplementation (eg. overnight gastrostomy/ nasogastric) but can
usually manage without parenteral support. Enteral supplements should be iso-osmolar and
high in salt – note that elemental diets are usually the opposite – hyperosmolar, low salt, and
may exacerbate fluid loss. Vitamin B12 supplementation is essential.
Question 5: For Medically Qualified Candidates
A man you discharged some years ago is referred by the GP back to your lipid clinic:
Age
Presentation
Exercise tolerance
Past medical history
Referral 1
57
Mixed
hyperlipidaemia
discovered during blood
donation
13
years
previously. Been on diet and
Clofibrate in the past, but no
treatment at present.
Walks for miles without ill
effect.
Occasional chest
tightness
and
difficulty
breathing brought on by
jarring
movements and
eased by leaning forward.
Has had attacks of gout in
the past
Referral 2
68
Lipid medication changed to
Simvastatin a few months ago:
lipids now worse.
Still a keen walker, but has
noticed some chest tightness
and ‘fizziness’ in his left arm
when walking uphill during a
monthly 8 mile hike with friends.
Recent urological investigations
after passing small blood clot in
urine; no pathology found.
Nifedipine m/r 30 mg bd
Simvastatin 40 mg nocte
Non-smoker from age 18.
One bottle of red wine per
week.
As before, plus: elder brother
died of MI at 68; younger
brother of 65 had MI last year;
sister of 60 on treatment for
hypertension. Sons of 40 and
38 not investigated.
Medications
Nil at present.
Smoking history
Alcohol intake
Non-smoker from age 18.
Six units per week.
Family history
Mother died of stroke at 65
after 4 year history of
angina. Father has gout.
One brother has peripheral
vascular
disease
and
hypertension. Sons of 29
and 27 not investigated.
Well.
No signs of lipid Well, apart from a small amount
deposition. BMI 28.7.
of
bilateral pitting
ankle
oedema. BMI 31.2.
190/110
170/110 (140/82 earlier in the
day on own BP meter!).
On examination
BP mm/Hg
Fasting lipids (mmol/L):
Cholesterol
Triglyceride
HDL cholesterol
Fasting plasma glucose
mmol/L
11.3
8.6
0.6
5.5
7.8
16.0
0.7
9.6
On the first occasion he was discharged on Bezafibrate 400 mg nocte and Nifedipine 30 mg
bd. His lipids then were cholesterol 6.5 mmol/L, triglycerides 3.9 mmol/L, HDL 0.8 mmol/L
and LDL 3.9 mmol/L, his BMI was 27.8 and his blood pressure 144/84
How would you investigate and manage this patient now?
If the first referral was being made now, would your investigation and management be any
different to what it was 11 years ago?
Question 5: Notes for Examiners
This clinical scenario is taken from a real case and should be familiar territory for anyone
who has worked in a lipid clinic. However, there is a lot of material here, so it is important for
candidates to prioritise their responses. I think the aspects to focus on first are as follows.
How would you investigate and manage this patient now?
The clinical history is suggestive of angina and needs further investigation.
positive exercise test, positive coronary angiography and is awaiting CABG.
He had a
Glucose: his fasting plasma glucose is in the diabetic range, although this was the first
raised glucose on record and he was asymptomatic. Further biochemical evidence was
sought (and readily obtained) to support the diagnosis. A dietitian gave appropriate dietary
advice.
Lipids: the Simvastatin is clearly not keeping his lipids within ideal limits. It was stopped and
he started Fenofibrate 267 mg nocte. After a couple of month he had managed to reduce
his BMI to 29.4 and the combination of this and the Fenofibrate improved his lipids to:
Cholesterol
Triglyceride
HDL
LDL
5.7 mmol/L
3.3 mmol/L
0.9 mmol/L
3.3 mmol/L
This is encouraging, but in view of his very high risk, a small dose (10 mg) of Simvastatin
was added back in (with appropriate warnings etc.), with further improvement in the profile
(non-fasting cholesterol 4.8 mmol/L).
Blood pressure etc: Nifedipine may have been implicated in his ankle oedema.
Currently on:
Ramipril
Atenolol
Nicorandil
Lansoprazole
Aspirin
Nitrolingual spray
2.5 mg daily
50 mg daily
10 mg bd
30 mg daily
75 mg daily
prn
plus lipid lowering drugs.
Family: his two sons should clearly be encouraged to have their lipids and other risk factors
checked.
If the first referral was being made now, would your investigation and management be any
different to what it was 11 years ago?
The way we assess risk, the evidence in favour of the benefits of risk factor management,
the drugs available and the targets of treatment have all changed over the years, so it is not
unreasonable to ask this question. It is more difficult for the author to be objective about his
own practice! However, some possible topics for discussion are:
Should the patient have had an exercise test at the first referral?
The lipids at discharge are not as good as current practice would wish.
I have heard it argued that everyone with raised triglycerides should have a glucose
tolerance test, irrespective of their fasting glucose. The rationale for this is that one would
be more likely to treat their hyperlipidaemia if the 2-hour glucose were raised. Since this
patient was treated anyway, it does not seem an important consideration here.
The two sons should have had a CHD risk factor assessment before now.
There are other biochemical markers of CHD risk that could have been checked, although I
am not convinced that the results would have made any difference to his management.
No one seems to have taken much interest in the management of his gout.
(NB. All the usual tests for secondary causes of hyperlipidaemia were negative).
Question 6
52 year old male bus driver presented with a 6 month history of increasing weakness.
He was previously healthy.
Weakness severe enough to require help.
He also complained of diarrhoea on and off for the past 4 months.
He also complained of generalised bone pain.
He is a non-smoker, does not drink alcohol.
Examination unremarkable except for muscle weakness – worse in proximal and lower
limbs.
Investigations
Renal function tests – normal.
Liver function tests – normal.
FBC – normal.
Calcium 2.28 (2.15-2.55) mmol/L
Phosphate 0.40 (0.80-1.30) mmol/L
ALP 376 (<126) IU/L
What further investigations would you recommend?
ALP isoenzyme studies showed ALP to be predominately of bone origin
TmP/GFR 0.23 (0.7-1.3) mmol/L
Serum PTH 25 (10-65) ng/L
Serum 250HD 82 (50-150) nmol/L
How do you interpret these results?
Suggest a possible diagnosis.
What advice would you give regarding the management of this patient?
Question 6: Information for Examiners
What further investigations would you recommend?
First confirm the low phosphate to exclude a transient decrease in phosphate due to
transcellular shift. Persistent low phosphate can cause muscle weakness.
Next step is to exclude vitamin D deficiency.
With a history of diarrhoea a malabsorption syndrome needs to be considered.
Faecal fat measurement was done and it was found to be normal.
Vitamin B12 and folate and full blood count were all normal.
Measurement of serum 250HD and PTH and renal tubular reabsorption of phosphate are
necessary.
How do you interpret these results?
Low TmP/GFR indicates reduced reabsorption of phosphate.
In vitamin D deficiency secondary hyperparathyroidism will cause low TmP/GFR and low
serum phosphate. Serum PTH and 250HD are within the reference range and this makes
vitamin D deficiency unlikely.
Suggest possible diagnosis.
Inherited hypophosphataemic disorder is unlikely – age and recent onset .
Oncogenic osteomalacia is the most likely diagnosis.
What advice would you give regarding the management of this patient?
Attempts to find the tumour were made and these were initially unsuccessful.
Treatment: Calcitriol and phosphate supplements. These improved symptoms and serum
phosphate increased to 0.7 mmol/L.
Questions for Clinical Scientists
Question 1
‘What action would you take when you discover that, due to a mechanical failure on a large
automated analyser involving specimen sequencing, 100 sets of general clinical
biochemistry results have been reported against the incorrect patient identities?’
The results had left the laboratory 36 hours previously and were from patients on medical
and surgical wards, and patients seen in outpatients, renal clinics and by general
practitioners.
Question 1: Notes for Examiners
The suggested action might be along the following lines:
1.
2.
3.
4.
5.
6.
7.
8.
9.
Inform all staff receiving requests for results over the phone, of the extent of the
problem, including the specimen accession numbers involved, and instruct them to
explain that these results are being rechecked. Where urgent clarification is need
recommend specimen recollection.
Identify correct results either by reanalysis or, where possible, reliable correction of
mismatched specimen and patient identity.
For each patient, compare correct with erroneous results, any previous results and the
source of the request.
Based on this information, ‘triage’ reports into those requiring immediate action
because of patient status and the magnitude or significance of the discrepancy. (eg.
preop/post op, time taken for report to reach user, such as computer report or hard
copy).
Attempt to contact medical staff and nursing staff concerned for high priority patients
identified above.
Amend computer database (both Lab and Hospital) with correct results. There is an
issue of transparency here so that accusations of a ‘cover up’ cannot be laid.
Issue amended hard copy reports with an explanatory comment regarding previous
erroneous results.
Investigate and document the circumstances of the incident following the local policy
for ‘Incident reporting’.
In addition to reviewing the mechanical failure and taking steps to prevent a repetition,
investigate how procedures for analytical validation and clinical credibility failed to
identify the error earlier.
Question 2
After many years of using a traditional wet chemistry analyser to provide the bulk of your
analyses, you are about to replace this with a modern discretionary analyser. The old
analyser required very frequent calibration; the manufacturers claim that each assay which is
run on the new analyser will only require calibration at intervals of 3 to 6 months.
Outline the internal quality control system you think appropriate to maintain the quality of
analyses on the new analyser.
Question 2: Notes for Examiners
Every candidate should know that classical internal QC techniques are designed to detect
unacceptably large changes in bias caused by calibration or reagent changes. In essence,
such techniques rely on deciding whether a QC signal (usually the result given by a QC
sample) lies within or outside a pre-set limit, which is usually a line drawn on a ‘QC chart’ (at
for example 3 SD away from the mean), often refined by further rules such as those
proposed by Westgard. The response to a result lying outside the limit is to re-calibrate and
possibly to change the reagents.
Every candidate should realise that the QC problems with modern analysers are different.
They are not about sudden stepwise changes in bias. They are about very slow changes in
bias with time (drift), about periods of deteriorating precision associated with less than
optimal analyser performance, and about occasional fliers. Candidates should realise that
classical QC techniques are inappropriate to these problems.
A more appropriate QC system must include:
1.
Checking whether bias is acceptable after calibration (eg. by comparison of QC results
or patient sample results before and after calibration).
2.
Monitoring very small bias changes over time, to decide the point at which recalibration is necessary.
A good candidate should point out that it is difficult to detect fliers, and this can usually only
be done by comparing results with previous results on that patient (delta checks) or by
comparing results with clinical information and/or with that is credible. The appropriate
response is of course to repeat the analysis.
An extremely good candidate may mention the problem of periods of increased imprecision.
There are several ways to look at this – the number of patient results falling outside the
reference range is often a good guide. The appropriate response to worsening imprecision
is to check instrument maintenance; and if necessary call the manufacturers in.
It may also be possible to push a good candidate into a discussion of what constitutes
acceptable performance, both for bias (particularly for hormone analyses) and for
imprecision (should be based on biological variation). Classical QC tends to be directed
towards technical achievability, not biochemical desirability.
Question 3
You are telephoned at home at 11.45 pm by a House Officer in the Accident and Emergency
Department, who would like an urgent blood ethanol measured on a 17 year old boy. He
has been involved in a road traffic accident, and the House Officer explains that the boy’s
parents are anxious to know the result.
What do you do?
Question 3: Notes for Examiners
This is a difficult real-life problem, and there are three distinct issues.
1.
Medical
In my view, the only medical justification for measuring ethanol in this case would be if
the patient had an altered state of consciousness, which could be related to ethanol or
could be related to a head injury. Knowledge of the ethanol concentration could
therefore affect subsequent medical assessment and treatment. If so, this is a justified
demand which could well be urgent. Without an altered state of consciousness, there
is no justification for measuring ethanol for medical reasons in this case.
2.
Legal
I think there are two main legal issues.
a. Confidentiality
1. The Victoria Gillick case established that even children of 15 have the right to
medical confidentiality. The House Officer must be told that any results, particularly
an ethanol result, should only be given to the parents if the patient agrees. Where
there is reason to believe that a crime has been committed, the police may obtain
authorisation to see medical records or seize samples – authorisation may be given
by for example a Coroner, a Judge, etc.
b. Assault
A blood sample which is potentially to be used for non-medical purposes can only
be taken from a patient if the patient agrees (or if unconsciousness, his next of kin
or other representative). I am unsure to what extent the parents of a minor can
give consent if the minor himself disagrees.
3.
Ethical
This is particularly difficult.
I personally believe that we should neither help nor hinder the police. However, where
there is reason to believe that a crime may have been committed, then there is a public
duty to ensure that as far as possible any relevant evidence is retained. In this case,
there are three main scenarios.
a. The patient is the driver of a motor vehicle. Potentially, a sample for blood ethanol
measurement could be instrumental in showing if he had driven while over the
statutory limit.
b. The patient is a pedestrian who was hit by a motor vehicle. The sample could then
be important evidence in a charge of dangerous driving by the driver of the vehicle.
c. The patient was a passenger in a motor vehicle. In this case, his blood ethanol is
likely to be irrelevant to any crime which may have been committed.
My own feeling is that if (a) or (b) apply, one should make an effort to obtain an
appropriate sample for blood ethanol measurement (although probably not to measure
it). However, to stay within the law, consent for this sample must be obtained from the
patient or his representative. It will be necessary to point out that in the event of a
crime, the result could help the prosecution or help the defence.
Question 4
You are contacted by a GP who wants to discuss the creatinine result on a full biochemical
profile on a 53 year old lady, and would like advice on further tests.
Na
K
Urea
Creatinine
Calcium
Phosphate
141
3.9
6.8
250
2.20
0.69
mmol/L
mmol/L
mmol/L
umol/L
mmol/L
mmol/L
Alkaline phosphatase
Total Protein
Albumin
Bilirubin
AST
148
69
39
7
27
U/L (RR<150)
g/L
g/L
umol/L
U/L (RR<50)
The clinical details given at the time were “Routine screen”. You note a previous creatinine
one month ago was 213 umol/L and that haematinics taken at that time were normal. In his
introduction the GP reveals that the lady had non-specific malaise with vague back and loin
pain but had no previous medical problems and had rarely bothered the surgery. One month
ago a haemoglobin of 9.7 g/dL with normochronic normocytic picture and ESR of 62 mm/h
had prompted the haematinic request and three faecal occult bloods were normal.
What information do you require from the GP and what further tests would you undertake on
this sample or suggest in the future?
Question 4: Notes for Examiners
This is a real case from last year. The lady obviously had some nephropathy but the
absence of a raised urea in the face of quite abnormal creatinine was very odd. The first
things I checked with the GP were that they had checked her BP and urinalysis – ie. was this
diabetic or hypertensive nephropathy. Her BP was normal and he thought urinalysis was
negative.
I then asked about drugs, concerned about a drug induced nephritis – she was using an
NSAID (I forget which) but not regularly. However I would want to try and draw out the
association of NSAID with nephritis and raised creatinine.
I was concerned at the time about some fliers on our creatinine method (Vitros dry slide) and
sent it for analysis a different way (Olympus – Jaffe). It came back identical.
I think it would be reasonable to suggest asking for a urine protein and MSU in view of her
symptoms in order to eliminate chronic nephritis but we never got to that stage as we got the
diagnosis on the sample we had.
I was then left with endogenous causes of nephropathy of which there are 3 easily
eliminated ones – myoglobin (no muscle symptoms except the vague back pain which could
have been renal), uric acid (but urea is usually elevated and no joint pains) and myeloma
proteins. I asked for a CK, forgot about uric acid, and despite the normal protein requested
an electrophoresis.
Electrophoresis showed a strong band which typed as free kappa light chains only with
immune paresis. This explains the lack of dipstick proteinuria and normal globulins. The
normal calcium was a good prognostic point (but the only one – her low urea was actually a
bad sign as it indicated massive anabolic activity and aggressive low grade disease). Had
we got round to measuring urine protein she had grams of pure Bence Jones protein in her
urine when worked up elsewhere by the haematologists.
This lady has an aggressive Bence Jones myeloma. She has had marrow ablation and a
transplant but has a very poor prognosis of less than 5 years survival.
Question 5
You have received a letter from NEQAS pointing out your poor performance in your plasma
urate assay. The letter states that your results have been very variable, with major biases
being seen either side of your method mean on different samples. Some recent NEQAS
returns are included in the following table.
Return Number
101
102
103
104
105
106
Method Mean
105
257
98
555
200
425
Your Result
133
265
129
434
211
357
Can you think of some possible explanations for these differences and explain how you
would investigate further?
Question 5: Notes for Examiners
From the NEQAS data it could be supposed that there may be a calibration problem, with
either the method group or your particular assay. It appears for high results your laboratory
is reporting results that are too low, and for low results your laboratory is reporting results
that are too high. At concentrations of urate of approximately 240-260 umol/L your
laboratory agrees with the consensus mean.
Possible actions:
ƒ
ƒ
ƒ
ƒ
ƒ
ƒ
ƒ
ƒ
Establish whether the correct results had been sent in.
Establish whether the laboratory has been put into the correct method group.
Establish from the NEQAS return whether the method mean is different to the other
reported method means.
Check your internal QC charts to check the precision, to see the amount of acceptable
variation you may expect for a serum urate assay (CV’s ~ 1-3%), ie. can the results be
explained by analytical variation. Do the charts show any variation over the measuring
range for urate?
Establish whether your laboratory performs the assay as per protocol, or whether you
use different calibrators, single-, multi-point, force-, do not force through zero.
The outcomes of these questions could lead you to think whether your laboratory is
“right” or “wrong”. It would be wrong to presume that the method mean is actually the
correct answer. Further action could range from doing some simple experiments to
contacting the company and NEQAS to discuss the problem.
Simple experiments could include “spiking” a sample with a known concentration of
urate (the candidates should think about how they would spike a sample with a high
concentration of urate), double diluting serum/control with saline (once again what
effects could this have, eg. matrix problems).
Time and money permitting you could check your method against an authenticated
standard, or get your friendly expert to measure some sample by isotope dilution MS.
You never know sometimes you can be right and they can be wrong!
Question 6
How would you assess a Laboratory’s performance?
Question 6: Notes for Examiners
Candidates should be able to come up with a range of answers, those sticking just to QC
and EQA should be encouraged to think wider.
EQA performance
ƒ Analytical
ƒ Clinical Comments
CPA
Error rates - Types of error (is it even measured?)
ƒ Clerical
ƒ Analytical
ƒ Clinical Authorisation
Good risk management with follow up of mistakes and near-misses
Turnaround times
Clinical Audit participation
How many calls to the duty biochemist are made per day
(Personal opinion is that if high indicates good use of Lab expertise, but open to argument)
Laboratory initiated and collaborative research
ƒ Publications
ƒ Research funding
Teaching
ƒ Biomedical Scientists
ƒ Clinical Scientists
ƒ Junior medical staff/medical students (if teaching hospital)
Feedback from users (CPA are particularly interested in this)
Others?